• Defects early in the pathway produce precursors which are neurotoxic and produce acute porphyrias. They show #autosomalDominant inheritance.
• More common are defects later on in the pathway cause accumulation of porphyrins leading to chronic porphyria; This is known as porphyria cutanea tarda.

[!TIP] Patient (esp. Female) with abdominal pain + neuropsychiatric features -> need to consider acute porphyria.

• Clinical features: Abdominal pain, neuropsychiatric features, seizures and fever.

• Can be precipitated by anaesthetic drugs and luteal phase of the menstrual cycle.

• Anaesthesia for suspected acute abdomen can be catastrophic.

• The defective enzyme in acute intermittent porphyria is porphobilinogen deaminase.

• The defect is in uroporphyrinogen decarboxylase.

• 80% of cases are acquired / sporadic; 20% are inherited.

• Uroporphyrinogen decarboxylase converts uroporphyrinogen III into coproporphyrinogen III.

• Presents with photosensitive blistering rash.

• Hypertrichosis and hyperpigmentation may be present.

• Liver disease is a common comorbidity:

  • Either caused by excessive hepatic porphyrins OR
  • liver disease due to hepatitic C / alcohol triggering porphyria.

• Triggers for attacks are caused by increased hepatic iron load but also alcohol, smoking, estrogens, hepatitis C or HIV.

• Phlebotomy - used to decrease the iron load.

• Hydroxycholorquine - increase the excretion of porphyrins.

    1. Overnight 1mg dexamethasone suppression test

• Primary adrenal insufficiency is also called Addison's disease
• Features: ⬇Na, ⬆K, ⬇pH
• Diagnosis
  • Screening: morning cortisol level.
  • confirmatory: Short synacthen test. (plasma cortisol is measure before and 30 minutes after administration of IM 250ug of Synacthen)
  • Other investigations (not related to Addison's disease):
    • 24 hour urinary free cortisol is used to check for cushing's syndrome; not Addison's.

Psoriatic arthritis is associated with HLA-B27.

Imaging

Psoriatic arthritis Vs. Rheumatoid arthritis

Differentiation is clinically important because prognosis and management are different.

Summary of enzymes involved

HMG-CoA reductase: Rate limiting enzyme in cholesterol sythesis : found in the liver and ? other tissues
LCAT : the enzyme synthesized by the liver and attached to HDL which exterifies cholesterol so that it becomes trapped inside HDL. Required for reverse transport of cholesterol.
LPL: lipoprotein lipase: the enzyme found on tissues which removes lipids from VLDL and it's derivatives, increasing their density.
If there is acidosis (pH < 7.2 or HCO3 < 15) or high ketonemia, manage as DKA.
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Endemic typhus serves as the prototype for pathogenesis:
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• [[Hormone Physiology#Adrenaline synthesis]]

Interface hepatitis is seen, just like autoimmune hepatitis.
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🔖Extrahepatic manifestations of hepatitis B

• Serum sickness like syndrome
• Oral lichen planus
• Papular acrodermatitis
• 
  • Which is also called ?Gianotti Crosti syndrome
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Symptoms : N/V, headache,
motor effects: nystagmus, tremor, cerebellar ataxia.

Phenytoin side effects

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